Non-invasive analysis is a valuable technique for acquiring information about systems or targets without undesirable side effects, such as damaging the system being analyzed. In the case of analyzing living entities, such as human tissue, undesirable side effects of invasive analysis include the risk of infection along with pain and discomfort associated with the invasive process. In the particular case of measurement of blood glucose levels in diabetic patients, it is highly desirable to measure the blood glucose level frequently and accurately to provide appropriate treatment of the diabetic condition as absence of appropriate treatment can lead to potentially fatal health issues, including kidney failure, heart disease or stroke. A non-invasive method would avoid the pain and risk of infection and provide an opportunity for frequent or continuous measurement.
Non-invasive analysis based on several techniques have been proposed. These techniques include: near infrared spectroscopy using both transmission and reflectance; spatially resolved diffuse reflectance; frequency domain reflectance; fluorescence spectroscopy; polarimetry and Raman spectroscopy. These techniques are vulnerable to inaccuracies due to issues such as, environmental changes, presence of varying amounts of interfering contamination, skin heterogeneity and variation of location of analysis. These techniques also require considerable processing to de-convolute the required measurement, typically using multi-variate analysis and have typically produced insufficient accuracy and reliability.
More recently optical coherence tomography (OCT), using a super-luminescence diode (SLD) as the optical source, has been proposed in Proceedings of SPIE, Vol. 4263, pages 83-90 (2001). The SLD output beam has a broad bandwidth and short coherence length. The technique involves splitting the output beam into a probe and reference beam. The probe beam is applied to the system to be analyzed (the target). Light scattered back from the target is combined with the reference beam to form the measurement signal.
Because of the short coherence length only light that is scattered from a depth within the target such that the total optical path lengths of the probe and reference are equal combine interferometrically. Thus the interferometric signal provides a measurement of the scattering value at a particular depth within the target. By varying the length of the reference path length, a measurement of the scattering values at various depths can be measured and thus the scattering value as a function of depth can be measured.
The correlation between blood glucose concentration and scattering has been reported in Optics Letters, Vol. 19, No. 24, Dec. 15, 1994 pages 2062-2064. The change of the scattering value as a function of depth correlates with the glucose concentration and therefore measuring the change of the scattering value with depth provides a measurement of the glucose concentration. Determining the glucose concentration from a change, rather than an absolute value provides insensitivity to environmental conditions.
However, SLDs emit incoherent light that consists of amplified spontaneous emissions with associated wide angle beam divergence which have the undesirable beam handling and noise problems. The beam is also a continuous wave (CW) source with no opportunity for temporal based signal enhancement. Also, because of the random nature of spontaneous emission, the reference signal must be derived from same SLD signal and have equal optical path length as the probe signal. Therefore, without an opportunity to avail of multiple sources, the relative optical path length must be physically changed by a scanning mechanism and the reference path length must be of similar magnitude to the probe path length. Typical electro-mechanical scanning techniques have limited scan speeds which makes conventional OCT systems critically vulnerable to relative motion between the analyzing system and the target. These aspects cause systems based on SLD sources to have significantly lower signal to noise characteristics and present problems in practical implementations with sufficient accuracy, compactness and robustness for commercially viable and clinically accurate devices.
Therefore there is an unmet need for commercially viable, compact, robust, non-invasive device with sufficient accuracy, precision and repeatability to measure analyte characteristics, and, in particular, to measure glucose concentration in human tissue.